The generation of hypotheses that can be tested in experimental systems is the goal of biochemical epidemiology. A major question concerns which particular genetic lesions might be important in carcinogenesis. In order to adequately answer this question it is logical to seek consistent genetic mutations in primary tumors and examine the effects of these lesions in normal or malignant cells in tissue culture. The establishment of a primary tumor panel that can be used to determine which gene mutations are worthy of further study or to determine particular spectra of mutations that may relate to specific exposures (e.g., cigarette smoking, coke oven or foundry effluent, coal smoke or cooking vapors) will be a valuable resource. Genetic polymorphisms that have been suggested to have an association with human cancer risk are the DNA-restriction fragment length polymorphisms (DNA-RFLPs) at the human HRAS1, L-myc and CYP2D6 loci. In the case of HRAS and L-myc, rare or minor restriction fragments (alleles) appear to either predispose to certain cancers or are associated with poor prognosis. There are no previous studies that have examined these markers within an epidemiological framework or a background of interlaboratory validation studies.